Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier

Brain-derived neurotrophic factor（BDNF） plays an important role in the repair of central nervous system injury,but cannot directly traverse the blood-brain barrier.Liposomes are a new type of non-viral vector,able to carry macromolecules across the blood-brain barrier and into the brain.Here,we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of liposomes conjugated to transferrin（Tf） and polyethylene glycol（PEG）,and carrying BDNF modified with cytomegalovirus promoter（pC MV） or glial fibrillary acidic protein promoter（p GFAP）（Tf-p CMV-BDNF-PEG and Tf-p GFAP-BDNF-PEG,respectively）.Both liposomes were able to traverse the blood-brain barrier,and BDNF was mainly expressed in the cerebral cortex.BDNF expression in the cerebral cortex was higher in the Tf-p GFAP-BDNF-PEG group than in the Tf-p CMV-BDNF-PEG group.This study demonstrates the successful construction of a non-virus targeted liposome,Tf-p GFAP-BDNF-PEG,which crosses the blood-brain barrier and is distributed in the cerebral cortex.Our work provides an experimental basis for BDNF-related targeted drug delivery in the brain.

Efficient Gene Targeting in Zebrafish Mediated by a Zebrafish-Codon-Optimized Cas9 and Evaluation of Off-Targeting Effect

Targeted genome modifications with the Cas9/gRNA system derived from the clustered regularly interspaced short palin- dromic repeat/CRISPR-associated （CRISPR/Cas） system have been successfully used in cultured human cells as well as in most model organisms, including zebrafish （Danio rerio）, mouse, and fruit fly （Chang et al., 2013; Cong et al., 2013; Gratz et al., 2013; Hwang et al., 2013; Jao et al., 2013; Shen et al., 2013; Wei et al., 2013）. Its application in zebrafish is particu- larly attractive due to the ease of handling this organism and the simple application of this method by direct injection of Cas9/ gRNA. However, the information about its specificity in this organism is very limited and needs further evaluation. In addition, it is conceivable that a Cas9 mRNA optimized for zebrafish codon preference could enhance its activity.

Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery

High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient cells.Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.

Enhancing Tax Administration Capacity Building in Developing Countries: A New Zealand Perspective

For developing countries,raising revenues and protecting their tax bases are more important than ever in recovering from the pandemic.As a small developed country,New Zealand endeavours to provide capacity building assistance to developing regions,especially the Pacific Islands.Assistance provided encompasses the development of core taxation systems as well as international tax matters such as the establishment of exchange of information programmes and the implementation of international tax standards.Working in partnership with international and regional organisations has proved beneficial,as demonstrated in the Pacific Initiative delivered over the last two years.Cost-effective and well-organised virtual delivery of training courses has functioned particularly well during the pandemic and will continue to feature prominently in future assistance work.